Acute myocardial infarction (heart attack) is a major cause of morbidity and mortality with a reported annual incidence of 1.1 million cases in the United States alone. It is despite the increasing use of cholesterol lowering agents and attentiveness to co-morbid illnesses. Subsequent to infarction, a variety of inflammatory and other changes are known to occur which despite proper reperfusion by thrombolytics and/or stenting, contribute to cardiac remodeling and eventual heart failure. Numerous other cardiac conditions are widely prevalent, particularly myocardial ischemia which is associated with atherosclerosis of arteries feeding myocardial tissue. Congenital and acquired cardiac abnormalities are numerous and range from valvular defects to hypertrophy to septal defects.
Cellular therapy of cardiovascular diseases has achieved some degree of success. For example, administration of autologous bone marrow stem cells has been demonstrated to benefit patients with end-stage chronic ischemic cardiomyopathy (1, 2). Additionally, administration of similar stem cell populations subsequent to the stunning phase of acute myocardial infarction has been demonstrated to induce an increase in left ventricular ejection fraction as compared to control patients (3). The methods by which stem cells induce therapeutic effect in cardiovascular diseases include induction of angiogenesis (4), inhibition of ventricular remodeling (5), and transdifferentiation into cardiomyocytes (6). Additionally, besides stem cells, skeletal muscle cells have also been used for treatment of cardiovascular diseases (7).
Numerous patents have been issued on utilizing stem cells for treatment of cardiovascular disease. For example, U.S. Pat. No. 7,166,280 entitled “Combination growth factor therapy and cell therapy for treatment of acute and chronic heart disease” teaches the combination of growth factor administration together with stem cell administration. Some of the growth factors mentioned in the patent have already been used for treatment of heart disease such as FGF and VEGF members. Additionally, it is important to note that others have already demonstrated synergy between administration of these types of growth factors together with stem cells. U.S. Pat. No. 6,387,369 entitled “Cardiac muscle regeneration using mesenchymal stem cells” discloses the use of mesenchymal stem cells for cardiac repair, specifically after myocardial infarction.
To date, no combination therapy has been reported that concurrently inhibits oxidative stress and administers stem cells. Although reports exist of utilizing nutritional intervention together with stem cell therapy (8), these do not induce substantive antioxidant effect. Given that stem cells are known to be sensitive to oxidative stress, the current invention provides, inter alia, a method of increasing efficacy of stem cell therapy through concurrent administration of antioxidants with said stem cell therapy.